The Challenges of Treating COVID-19: Lessons from Gilead’s Remdesivir

(Posted on Monday, January 10, 2022)

As COVID-19 infections continue to peak, researchers around the world are working at unprecedented speeds to manufacture disease prevention and treatment options to combat the ever-growing list of COVID-19 variants. Several candidates have been identified for emergency use authorization, including monoclonal antibodies, but the current surge of infections suggests that the emerging Omicron variant is already resistant to current treatments and vaccines. The administration of these antiviral treatments, particularly to immunocompromised patients, has consequently created new drug-resistant mutations to the viral genome. Researchers in Australia, for example, found that patients treated with sotrovimab, a monoclonal antibody therapy, displayed rapid changes in the viral genome and the emergence of new variants. Although current treatments against COVID-19 are unable to slow the spread of infection, several candidates have been beneficial in preventing individuals at high risk of severe disease from being hospitalized. In particular, remdesivir, brand name Velurky, gained significant coverage in the early months of the pandemic as the first and only FDA approved antiviral treatment for COVID-19.

Authorized for adults and children 12 years and older, intravenous doses of remdesivir have been shown to shorten recovery time for hospitalized patients by 5 days. Administration to children under 12 years old has not gained full approval, but the drug is authorized for emergency use for hospitalized pediatric patients.

Laboratory studies demonstrate that remdesivir acts as a nucleoside ribonucleic acid (RNA) polymerase inhibitor against the Covid-19 virus. Simply put, the antiviral drug works by preventing replication of viral RNA in infected cells, which stops the virus from multiplying. In a majority Covid-19 cases, the body produces a substantial immune response that slows the spread of infection without the need for medication. Among individuals with significant comorbidities or other risk factors that weaken immune response, however, treatments like remdesivir help the body to fight infection, preventing the progression of severe complications or death.

For those at risk of developing severe disease, treatment with remdesivir at early mild to moderate stages of infection could significantly halt disease progression. Starting treatment at the first indication of Covid-19 infection, therefore, would reduce hospitalizations and lessen the strain on our healthcare system.

In a recent study published in the New England Journal of Medicine, researchers at the Baylor University Medical Center in Dallas, TX and affiliated institutions found that a three-day course of remdesivir lowered the risk of hospitalization by 87.5% in symptomatic, non- hospitalized Covid-19 patients. Participants met the recruitment criteria if the onset of their symptoms was within the previous 7 days and if they had at least one risk factor for developing severe disease, including pre-existing conditions and age over 60 years. The most common pre-existing conditions were obesity, diabetes, and hypertension. Among the 562 total participants, 0.7% of patients receiving remdesivir were hospitalized or died due to Covid-19-related complications, compared to 5.3% in the placebo groups. Researchers are optimistic that remdesivir may play an important role in the campaign to end the Covid-19 pandemic.

Eligibility restrictions and safety concerns for certain vulnerable groups, however, narrows the strength of remdesivir’s effectiveness within the larger population. Although the FDA previously determined that remdesivir has an acceptable benefit to risk ratio, studies have yet to consider its efficacy and safety for treating vaccinated individuals and against new variants of concern, including Delta and Omicron. Remdesivir may not in fact be the silver bullet that halts the pandemic.

Clinical studies warn that this antiviral drug may induce mild to moderate inflammation of the liver evident by increased enzyme levels. Therefore, remdesivir is not recommended for patients with liver disease or chronic kidney disease, which dysregulates the body’s ability to expel toxins and results in damage to the liver. Remdesivir’s effect on the liver also disqualifies patients taking medications with known side effects to the liver. This includes a wide range of common medications, such as certain steroids, birth control pills, drugs to treat high cholesterol, antibiotics and even over the counter drugs like Tylenol. Many of these drugs are routinely taken together to treat a multitude of conditions, especially among older populations. However, possible interactions with remdesivir may prohibit millions of people at high risk of Covid-19 complications from receiving treatment.

Remdesivir may also be inaccessible for patients that do qualify for treatment. Clinical studies indicate that this antiviral treatment works best as a three-day intravenous course. Therefore, non-hospitalized patients would need to travel to health centers with the equipment needed for an IV and available supply of remdesivir. Also, having to return for two additional days of treatment increases the burden on symptomatic individuals, as well as the health professions risking exposure. To combat these limitations, alternative methods for administering remdesivir should be considered, such as oral pills that could be taken from home.

In the midst of this pandemic, we do not have the luxury of time. Many of the outstanding questions related to remdesivir’s efficacy, safety and accessibility can only be answered with increased clinical trials and case studies, requiring a great deal of time and resources. As long as the Covid-19 virus continues to spread globally, weaknesses in the current campaign to prevent infection may facilitate the emergence of mutations resistant to treatment. Therefore, the race is on to manufacture and approve additional treatments with multidimensional approaches for fighting Covid-19. In the meantime, the most effective strategy for slowing the pandemic includes increasing accessibility to testing, so that patients at high risk for severe disease are treated as early as possible.

Read the full article on Forbes.